Salome Erhardt

Improved microsurgical creation of venous pouch arterial bifurcation aneurysms in rabbits.

BACKGROUND AND PURPOSE: The choice of the experimental aneurysm model is essential for valid embolization-device evaluations. So far, the use of the rabbit venous pouch arterial bifurcation aneurysm model has been limited by demanding microsurgery, low aneurysm patency rates, and high mortality. This study aimed to facilitate microsurgery and to reduce mortality by optimized peri-/postoperative management. MATERIALS AND METHODS: Aneurysms were created in 16 New Zealand white rabbits under general intravenous anesthesia. Using modified microsurgical techniques, we sutured a jugular vein pouch into a bifurcation created between both CCAs. Aggressive anticoagulation (intraoperative intravenous: 1000-IU heparin, 10-mg acetylsalicylic acid/kg; postoperative subcutaneous: 14 days, 250-IU/kg /day heparin) and prolonged postoperative anesthesia (fentanyl patches: 12.5 μg/h for 72 hours) were applied. Angiographic characteristics of created experimental aneurysms were assessed. RESULTS: The reduced number of interrupted sutures and aggressive anticoagulation caused no intra-/postoperative bleeding, resulting in 0% mortality. Four weeks postoperation, angiography showed patency in 14 of 16 aneurysms (87.5%) and Ohshima type B bifurcation geometry. Mean values of parent-artery diameters (2.3 mm), aneurysm lengths (7.9 mm), and neck widths (4.1 mm) resulted in a mean 1.9 aspect ratio. CONCLUSIONS: Compared with historical controls, the use of modified microsurgical techniques, aggressive anticoagulation, and anesthesia resulted in higher aneurysm patency rates and lower mortality rates in the venous pouch arterial bifurcation aneurysm model. Gross morphologic features of these aneurysms were similar to those of most human intracranial aneurysms.

The Rabbit Shunt Model of Subarachnoid Haemorrhage

Aneurysmal subarachnoid haemorrhage (SAH) is a disease with devastating complications that leads to stroke, permanent neurological deficits and death. Clinical and ex-perimental work has demonstrated the importance of the contribution of delayed cerebral vasospasm (DCVS) indepen-dent early events to mortality, morbidity and functional out-come after SAH. In order to elucidate processes involved in early brain injury (EBI), animal models that reflect acute events of aneurysmal bleeding, such as increase in intracranial pressure (ICP) and decrease in cerebral perfusion pressure, are needed. In the presented arterial shunt model, bleeding is initially driven by the pressure gradient between mean arterial blood pressure and ICP. SAH dynamics (flow rate, volume and duration) depend on physiological reactions and local anatomical intrathecal (cistern) conditions. During SAH, ICP reaches a plateau close to diastolic arterial blood pressure and the blood flow stops. Historical background, anaesthesia, perioperative care and monitoring, SAH induction, technical considerations and advantages and limitations of the rabbit blood shunt SAH model are discussed in detail. Awareness of technical details, physiological characteristics and appropriate monitoring methods guarantees successful implementation of the rabbit blood shunt model and allows the study of both EBI and DCVS after SAH.

Complex Bilobular, Bisaccular, and Broad-Neck Microsurgical Aneurysm Formation in the Rabbit Bifurcation Model for the Study of Upcoming Endovascular Techniques

BACKGROUND AND PURPOSE: Despite rapid advances in the development of materials and techniques for endovascular intracranial aneurysm treatment, occlusion of large broad-neck aneurysms remains a challenge. Animal models featuring complex aneurysm architecture are needed to test endovascular innovations and train interventionalists. MATERIALS AND METHODS: Eleven adult female New Zealand rabbits were assigned to 3 experimental groups. Complex bilobular, bisaccular, and broad-neck venous pouch aneurysms were surgically formed at an artificially created bifurcation of both CCAs. Three and 5 weeks postoperatively, the rabbits underwent 2D-DSA and CE-3D-MRA, respectively. RESULTS: Mortality was 0%. We observed no neurologic, respiratory, or gastrointestinal complications. The aneurysm patency rate was 91% (1 aneurysm thrombosis). There was 1 postoperative aneurysm hemorrhage (9% morbidity). The mean aneurysm volumes were 176.9 ± 63.6 mm3, 298.6 ± 75.2 mm3, and 183.4 ± 72.4 mm3 in bilobular, bisaccular, and broad-neck aneurysms, respectively. The mean operation time was 245 minutes (range, 175–290 minutes). An average of 27 ± 4 interrupted sutures (range, 21–32) were needed to create the aneurysms. CONCLUSIONS: This study demonstrates the feasibility of creating complex venous pouch bifurcation aneurysms in the rabbit with low morbidity, mortality, and high short-term aneurysm patency. The necks, domes, and volumes of the bilobular, bisaccular, and broad-neck aneurysms created are larger than those previously described. These new complex aneurysm formations are a promising tool for in vivo animal testing of new endovascular devices.

Outer skull landmark-based coordinates for measurement of cerebral blood flow and intracranial pressure in rabbits

Despite the increased use of intracranial neuromonitoring during experimental subarachnoid hemorrhage (SAH), coordinates for probe placement in rabbits are lacking. This study evaluates the safety and reliability of using outer skull landmarks to identify locations for placement of cerebral blood flow (CBF) and intraparenchymal intracranial pressure (ICP) probes. Experimental SAH was performed in 17 rabbits using an extracranial-intracranial shunt model. ICP probes were placed in the frontal lobe and compared to measurements recorded from the olfactory bulb. CBF probes were placed in various locations in the frontal cortex anterior to the coronary suture. Insertion depth, relation to the ventricular system, and ideal placement location were determined by post-mortem examination. ICP recordings at the time of SAH from the frontal lobe did not differ significantly from those obtained from the right olfactory bulb. Ideal coordinates for intraparenchymal CBF probes in the left and right frontal lobe were found to be located 4.6±0.9 and 4.5±1.2 anterior to the bregma, 4.7±0.7mm and 4.7±0.5mm parasagittal, and at depths of 4±0.5mm and 3.9±0.5mm, respectively. The results demonstrate that the presented coordinates based on skull landmarks allow reliable placement of intraparenchymal ICP and CBF probes in rabbit brains without the use of a stereotactic frame.

Microsurgical Venous Pouch Arterial-Bifurcation Aneurysms in the Rabbit Model: Technical Aspects

For ruptured human cerebral aneurysms endovascular embolization has become an equivalent alternative to aneurysm clipping.(1) However, large clinical trials have shown disappointing long-term results with unacceptable high rates of aneurysm recanalization and delayed aneurysm rupture.(2) To overcome these problems, animal experimental studies are crucial for the development of better endovascular devices.(3-5) Several animal models in rats, rabbits, canines and swine are available.(6-8) Comparisons of the different animal models showed the superiority of the rabbit model with regard to hemodynamics and comparability of the coagulation system and cost-effectiveness.(9-11) The venous pouch arterial bifurcation model in rabbits is formed by a venous pouch sutured into an artificially created true bifurcation of both common carotid arteries (CCA). The main advantage of this model are true bifurcational hemodynamics.(12) The major drawbacks are the sofar high microsurgical technical demands and high morbidity and mortality rates of up to 50%.(13) These limitations have resulted in less frequent use of this aneurysm model in the recent years. These shortcomings could be overcome with improved surgical procedures and modified peri- and postoperative analgetic management and anticoagulation.(14-16) Our techniques reported in this paper demonstrate this optimized technique for microsurgical creation of arterial bifurcation aneurysms.

3D computerized occlusion rating of embolized experimental aneurysms using noninvasive 1.5T MR imaging.

BACKGROUND AND PURPOSE: For embolized cerebral aneurysms, the initial occlusion rate is the most powerful parameter to predict aneurysm rerupture and recanalization. However, the occlusion rate is only estimated subjectively in clinical routine. To minimize subjective bias, computer occlusion-rating (COR) was successfully validated for 2D images. To minimize the remaining inaccuracy of 2D-COR, COR was applied to 1.5T 3D MR imaging. MATERIALS AND METHODS: Twelve experimental rabbit aneurysms were subjected to stent-assisted coil embolization followed by 2D DSA and 3D MR imaging. Subjective occlusion-rate (SOR) was estimated. Linear parameters (aneurysm length, neck width, parent vessel diameter) were measured on 2D DSA and 3D MR imaging. The occlusion rate was measured by contrast medium−based identification of the nonoccluded 2D area/3D volume in relation to the total aneurysm 2D area/3D volume. 2D and 3D parameters were statistically compared. RESULTS: There were no limiting metallic artifacts by using 3D MR imaging. Linear parameters (millimeters) were nearly identical on 2D DSA and 3D MR imaging (aneurysm length: 7.5 ± 2.6 versus 7.4 ± 2.5, P = .2334; neck width: 3.8 ± 1.0 versus 3.7 ± 1.1, P = .6377; parent vessel diameter: 2.7 ± 0.6 versus 2.7 ± 0.5, P = .8438), proving the high accuracy of 3D MR imaging. COR measured on 3D MR imaging was considerably lower (61.8% ± 26.6%) compared with the following: 1) 2D-COR (65.6% ± 27.1%, P = .0537) and 2) 2D-SOR estimations (69.2% ± 27.4%, P = .002). These findings demonstrate unacceptable bias in the current clinical standard SOR estimations. CONCLUSIONS: 3D-COR of embolized aneurysms is easily feasible. Its accuracy is superior to that of the clinical standard 2D-SOR. The difference between 3D-COR and 2D-COR approached statistical significance. 3D-COR may add objectivity to the ability to stratify the risk of rerupture in embolized cerebral aneurysms.

Long-term patency of complex bilobular, bisaccular, and broad-neck aneurysms in the rabbit microsurgical venous pouch bifurcation model.

Abstract Objectives: In experimental aneurysm models, long-term patency without spontaneous thrombosis is the most important precondition for analyses of embolization devices. We recently reported the feasibility of creating complex venous pouch bifurcation aneurysms in the rabbit with low morbidity, low mortality, and high short-term aneurysm patency. In order to further evaluate our model, we examined the long-term patency rate. Methods: Various sizes of complex bilobular, bisaccular, and broad-neck venous pouch aneurysms were surgically formed at an artificially created bifurcation of both common carotid arteries in 17 rabbits. Early aggressive anticoagulation was continued for 1 month. The rabbits were followed up using contrast-enhanced three-dimensional 1·5-T magnetic resonance angiography (CE-3D-MRA) at 1 month and up to 1 year after creation of the bifurcation. Results: At 1-month follow-up, all but one of the created aneurysms and all parent vessels proved to be patent. Three animals (18%) were lost during follow-up for reasons unrelated to aneurysm surgery. At 1-year follow-up, one animal showed partial and one complete spontaneous aneurysm thrombosis (aneurysm patency rate: 86%). Six out of 42 parent vessels were occluded at that time (vessel patency rate: 86%). Conclusions: Complex bilobular, bisaccular, and broad-neck microsurgical aneurysm formation in the rabbit bifurcation model demonstrates a high long-term patency rate but is complicated by high rates of unrelated procedural mortality and morbidity. There is no need for prolonged (>4 weeks) anticoagulation to achieve good long-term patency in complex venous pouch bifurcation aneurysms.

Comparison between routine cylindrical cerebral aneurysm volume approximation and three-dimensional volume measurements in experimental aneurysms

Abstract Objectives: Aneurysm volume is routinely approximated calculating cylindrical volumes. Exact aneurysm volume assessment is crucial for liquid polymer embolization. The aim of this study was to compare simple cylindrical volume approximations with direct multiplanar reconstruction (MPR) segmentational volumetry in a saccular/complex experimental rabbit bifurcation aneurysm model. Methods: In 12 female New Zealand white rabbits, saccular, broad-based, bilobular, and bisaccular aneurysms (three of each) were created using the rabbit venous pouch bifurcation model. Contrast-enhanced magnetic resonance angiography (CE-MRA) was performed, and maximal intensity projection (MIP) reconstructions as well as an MPR dataset were acquired. Aneurysm width and length were measured in MIP images, and the volume was approximated calculating cylindrical volumes. Three-dimensional (3D) segmentational volumetry using the MPR dataset was performed in a semi-automated manner. Results: Maximal intensity projection cylindrical volumes ranged from 53·6 to 503·5 mm3 (mean 186·5±118 mm3). Multiplanar reconstruction segmentation-based volumes ranged from 74·7 to 581·0 mm3 (mean 202·2±133 mm3). The mean relative difference between MIP cylindrical and MPR segmentation volume calculation was 24·7% (range −77·5 to +50·8%). Only 4 of 12 MPR segmentational volumes were within a 10% range of results calculated for MIP cylindrical volume, and 3 of those were in broad-based aneurysms. Conclusion: This descriptive study demonstrates that estimated MIP cylindrical volumes differ from those measured by MPR segmentation volumetry. With the increasing acquisition of 3D data as 3D-MRA and the increasing need for exact volume determination, studies on the accuracy of computational segmentational volumetry of CE-MRA are necessary.

A microsurgical bifurcation rabbit model to investigate the effect of high-intensity focused ultrasound on aneurysms: a technical note

BackgroundRecent clinical studies confirmed the high potential of MR-guided focused ultrasound (MRgFUS) in the field of functional neurosurgery. While its ability for precise thermo-ablation within soft tissue is widely recognized, the impact of high-intensity focused ultrasound (HIFU) on larger vessels is less explored. We used a bifurcation aneurysm model in rabbits to investigate the possible effects on the walls of vascular aneurysms and to assess the risk and prospect of this procedure for managing neurovascular disorders.MethodsExperimental bifurcation aneurysms were microsurgically created in New Zealand white rabbits and sonicated using MRgFUS.ResultsA temperature of max. 54°C could be achieved close to the aneurysm, and the shape and size of the aneurysm were noticeably changed, as shown by MR angiography.ConclusionsThe presented rabbit model proved suitable and capable of being extended to acquire data on the effect of HIFU on aneurysms and larger vessels. The fact that HIFU led to an alteration of the aneurysm without inducing rupture encourages further investigations.